Transforming Growth Factor-β (TGF-β) Signaling Inhibitors in Cancer Therapy

  • Pran K. Datta
  • Jason R. Mann
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Discovery of molecular pathways critical to carcinogenesis is revolutionizing the treatment and prevention of cancer. Traditional chemotherapeutic approaches involve “global” cytotoxicity to both normal and carcinoma cells. Over the past decade, investigators have developed compounds that are selective in inhibiting tumor formation by targeting specific signaling pathways, including transforming growth factor-β (TGF-β). The TGF-β family of polypeptides controls a broad spectrum of biological processes including proliferation, differentiation, apoptosis, and extracellular matrix production. While downstream signaling events have been extensively studied over the past two decades, perhaps the most interesting and significant advances of the next decade will involve therapeutic modulation of TGF-β signaling. Under transforming conditions, tumor cells are relieved from TGF-β-induced growth constraints and an increased production of TGF-β creates a local immunosuppressive environment that promotes tumor growth and worsens the invasive and metastatic behavior of the tumor. Therefore, counteracting the tumor-promoting effects of TGF-β presents a novel potential application of these inhibitors as therapeutic agents for human cancers with the goal of blocking tumor invasion, angiogenesis, and metastasis. The significant challenge involves identifying appropriate patients for therapy to ensure that targeted tumors are not only refractory to TGF-β-induced tumor-suppressor functions but also responsive to tumor-promoting effects of TGF-β. This report reviews our current understanding of TGF-β signal transduction with a particular focus on therapeutic modulation of TGF-β signaling in human cancers.

Key Words

TGF-β small-molecule inhibitors signal transduction tumor suppressor tumor promoter biomarker cancer therapy 
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Copyright information

© Humana Press Inc., Totowa, NJ 2008

Authors and Affiliations

  • Pran K. Datta
    • 1
  • Jason R. Mann
    • 1
  1. 1.Departments of Surgery and Cancer Biology, Vanderbilt-Ingram Cancer CenterVanderbilt University School of MedicineNashvilleUSA

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